On the basis of a mathematical analysis of the time course of the drug distributed in the organism there were studied pharmacokinetics of antituberculosis drugs after an isolated oral administration of doses used in daily treatment of tuberculosis, in INH, RMP, EMB, PZA, ETA, CS and TZ, and after a simultaneous--single and repeated--administration of INH, RMP, EMB in a triple combination, after the usual daily doses and after increased intermittent doses administered twice weekly. At first there were determined, with the use of chemical methods, blood concentrations of the antituberculosis drugs studied and their excretion with urine in an unchanged form. The results were analyzed pharmacokinetically by means of a one- compartment model with absorption. By an iteration process, based on non-linear regression analysis, the following pharmacokinetic parameters were calculated: Vd, Ka, Ke, T0.5 abs, T0.5 el, Tmax, Cmax, Clp tot and AUC. Their comparison revealed the following facts: The microbiologically most effective antituberculosis drugs--INH and RMP--are comparable even from the point of view of pharmacokinetics on account of similar pharmacokinetic parameters; in comparison with them EMB has half the size of the AUC, characterizing the efficacy of the drug. In this parameter PTA exceeds more than twice ETA; CS and TZ have a low Ke as well as Clp tot and a high T0.5 el, which is indicative of an insufficient excretion of both drugs. Pharmacokinetic parameters of PZA confirm the possibility of using the dose of 25 mg/kg in the treatment of tuberculosis. A simultaneous administration of the triple drug combination under study influences pharmacokinetic parameters of all the three antituberculosis drugs--it significantly decreases Ka as well as Ke, increases T0.5 el, Tmax, Vd and in INH also Clp tot, but only after a repeated administration. An intermittent administration of the mentioned triple drug combination significantly increases the area under the curve AUC in all the three antituberculosis drugs. This explains the same efficacy of higher doses of antituberculosis drugs, administered twice weekly, in comparison with a daily administration of lower doses of the same combination. The pharmacokinetic process of orally administered antituberculosis drugs can be analyzed according to a one-compartment model of pharmacokinetics, although the kinetics of certain antituberculosis drugs probably proceed in the organism in a more complicated way.

• MeSH
• antituberkulotika aplikace a dávkování   metabolismus   MeSH
• aplikace orální MeSH
• dospělí MeSH
• ethambutol aplikace a dávkování   MeSH
• isoniazid aplikace a dávkování   MeSH
• kinetika MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• plicní tuberkulóza farmakoterapie   metabolismus   MeSH
• rifampin aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antituberkulotika MeSH
• ethambutol MeSH
• isoniazid MeSH
• rifampin MeSH

Bioavailability increasing of poorly soluble drugs has become one of the main topics of modern pharmaceutical technology. Many methods based on the chemical modification, physical modification or new technological processes have been already used to improve bioavailability. Some of these methods (e.g. micronization, preparation of solid dispersions, formulation of an inclusion complex, etc.) have been for many years successfully used by pharmaceutical companies. On the other hand, methods such as liquisolid system and self-emulsifying drug delivery systems are still in the early stages of their development. It is expected that this novel methods could play a significant role in the preparation of modern dosage forms. The aim of this paper is to provide the summary of methods improving bioavailability of poorly soluble drugs used in the field of pharmaceutical technology.

• MeSH
• aplikace orální MeSH
• biologická dostupnost MeSH
• chemie farmaceutická MeSH
• farmaceutická technologie metody   MeSH
• lidé MeSH
• rozpustnost MeSH
• systémy cílené aplikace léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• IODINE/administration *, ION TRANSFER *, PROCAINE/administration *,
• MeSH
• iontoforéza * MeSH
• iontová výměna * MeSH
• jod aplikace a dávkování   MeSH
• léčivé přípravky * MeSH
• lidé MeSH
• prokain aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• jod MeSH
• léčivé přípravky * MeSH
• prokain MeSH

Methamphetamine abuse imposes a significant burden on individuals and society worldwide, and an effective therapy of methamphetamine addiction would provide distinguished social benefits. Ghrelin significantly participates in reinforcing neurobiological mechanisms of stimulants, including amphetamines; thus, ghrelin antagonism is proposed as a promising addiction treatment. The aim of our study was to elucidate whether the pretreatment with growth hormone secretagogue receptor (GHS-R1A) antagonist, substance JMV2959, could reduce the methamphetamine intravenous self-administration (IVSA) and the tendency to relapse, and whether JMV2959 could reduce or prevent methamphetamine-induced conditioned place preference (CPP) in rats. Following an adequate maintenance period, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 180 min sessions of methamphetamine IVSA under a fixed ratio FR1, which significantly reduced the number of active lever-pressings, the number of infusions, and the amount of the consumed methamphetamine dose. Pretreatment with JMV2959 also reduced or prevented relapse-like behavior tested in rats on the 12th day of the abstinence period. Pretreatment with JMV2959 significantly reduced the expression of methamphetamine-induced CPP. Simultaneous administration of JMV2959 with methamphetamine during the conditioning period significantly reduced the methamphetamine-CPP. Our results encourage further research of the ghrelin antagonism as a potential new pharmacological tool for methamphetamine addiction treatment.

• Klíčová slova
• addiction, conditioned place preference, ghrelin antagonism, intravenous self-administration, methamphetamine, rat,
• MeSH
• analýza rozptylu MeSH
• autoaplikace MeSH
• časové faktory MeSH
• glycin aplikace a dávkování   analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• methamfetamin aplikace a dávkování   farmakologie   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• potkani Wistar MeSH
• prostorové chování účinky léků   MeSH
• receptory ghrelinu antagonisté a inhibitory   metabolismus   MeSH
• stimulanty centrálního nervového systému aplikace a dávkování   farmakologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• triazoly aplikace a dávkování   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glycin MeSH
• methamfetamin MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• receptory ghrelinu MeSH
• stimulanty centrálního nervového systému MeSH
• triazoly MeSH

AIM: To determine the most effective administration of tranexamic acid (TXA) in patients with primary total knee arthroplasty (TKA). MATERIAL AND METHOD: We enrolled a total of 400 patients (154 men and 346 women) in this randomized trial (4 groups, each of 100 patients). The first group (IV1) had a single intravenous dose (15 mg TXA/kg) prior to skin incision. Group 2 (IV2) had TXA in 2 intravenous doses (15 mg TXA/kg): prior to skin incision and 6 hours after the first dose. Group 3 (TOP) had 2 g TXA in 50 mL of saline irrigated topically at the end of the surgery. The fourth group (COMB) combined IV1 and TOP regimens. We monitored the amount of total blood loss (TBL), haemoglobin drop, use of blood transfusions (BTs), and complications in each patient. RESULTS: The amount of TBL was significantly lower in IV1, IV2 and COMB regimens compared to the TOP (P<0.0001). The lowest decrease in haemoglobin within 12 hours after surgery was observed in intravenous regimens (P=0.045). A significant difference in haemoglobin decrease on day 1 after the surgery was demonstrated in the COMB and intravenous regimens (P=0.011). CONCLUSION: In primary TKA, it is preferable to administer TXA intravenously in two doses or in a combined regimen. Simple topical administration of TXA was not as effective and is indicated only in cases where systemic administration of TXA is contraindicated. No substantial complications occurred in either group of patients.

• Klíčová slova
• combined administration, intravenous administration, randomized clinical trial, topical administration, total knee arthroplasty, tranexamic acid,
• MeSH
• antifibrinolytika * MeSH
• aplikace lokální MeSH
• intravenózní podání MeSH
• krvácení při operaci prevence a kontrola   MeSH
• kyselina tranexamová * MeSH
• lidé MeSH
• totální endoprotéza kolene * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antifibrinolytika * MeSH
• kyselina tranexamová * MeSH

Sublingual administration of active pharmaceutical substances is in principle favourable for rapid onset of drug action, ready accessibility and avoidance of first pass metabolism. This administration could prove very useful in the treatment of migraines, thus two frequently used drugs were selected for our study. Sumatriptan succinate, naproxen, and its salt as well as combinations of these were incorporated into nanofibrous membranes via the electrospinning process. DSC measurements proved that the resulted membranes contained non-crystalline drug forms. SEM imaging approved good homogeneity of diameter and shape of the membrane nanofibres. The nanofibrous membranes always showed the rapid and mutually independent release of the tested drugs. The drugs exhibited very high differences in sublingual permeation rates in vitro, but the rates of both substances were increased several times using nanofibrous membranes as the drug carrier in comparison to drug solutions. The released drugs subsequently permeated through sublingual mucosa preferentially as non-ionized moieties. The prepared nanofibrous membranes proved very flexible and mechanically resistant. With their drug load capacity of up to 40% of membrane mass, they could be very advantageous for the formulation of sublingual drug delivery systems.

• Klíčová slova
• Electrospinning, Migraine, NAP, NAPS, Nanofibre, Naproxen, SUS, Sublingual, Sumatriptan, naproxen, naproxen sodium, sumatriptan succinate,
• MeSH
• antiflogistika nesteroidní aplikace a dávkování   chemie   MeSH
• aplikace sublinguální MeSH
• nanovlákna chemie   MeSH
• naproxen aplikace a dávkování   chemie   MeSH
• prasata MeSH
• sumatriptan aplikace a dávkování   chemie   MeSH
• systémy cílené aplikace léků * MeSH
• techniky in vitro MeSH
• ústní sliznice metabolismus   MeSH
• vazokonstriktory aplikace a dávkování   chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• naproxen MeSH
• sumatriptan MeSH
• vazokonstriktory MeSH

GC with nitrogen phosphorus detection and HPLC with UV detection were used to determine midazolam (MDZ) levels in rabbit plasma following ocular and nasal administration. For GC with nitrogen phosphorus detection, the analyte was extracted from the plasma using a three-step liquid-liquid extraction including extraction with an isopropanol/butyl chloride mixture in an alkaline solution, followed by extractions with 1 M HCl, and finally with an alkaline solution of butyl chloride. The recovery of MDZ was dependent on the sample alkalization time prior to the final extraction. The procedure increased the recovery of MDZ up to 99.6%. Improved sample preparation led to a significant increase in the sensitivity of the determination by GC with nitrogen phosphorus detection. The achieved detection limit was 0.34 ng/mL, which is ten times lower than that obtained using HPLC with UV detection. The small plasma volume was another advantage of the GC with nitrogen phosphorus detection method (200 μL per assay). Both administration routes of the anesthetic (nasal and ocular) resulted in comparable plasma MDZ levels. Kinetic simulation of the MDZ plasma was performed for both administration routes.

• Klíčová slova
• Fentanyl, Midazolam, Nasal administration, Nitrogen phosphorus detection, Ocular administration,
• MeSH
• aplikace intranazální MeSH
• aplikace oční MeSH
• chromatografie plynová metody   MeSH
• hypnotika a sedativa aplikace a dávkování   krev   MeSH
• králíci MeSH
• limita detekce MeSH
• midazolam aplikace a dávkování   krev   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hypnotika a sedativa MeSH
• midazolam MeSH

Patients who are unable to receive oral medication (p.o.) are a major problem in outpatient settings, especially in home health care systems. Mucosal administration of drugs offers an alternative to the oral route, especially when the parenteral mode cannot be used. There are three main pathways of mucosal administration: sublingual/buccal, intranasal and rectal. We discuss the possibility of mucosal delivery of antihypertensive drugs. Perindopril arginine and Amlodipine besylate are registered in the EU as orodispersible tablets for oromucosal delivery, however, they are not available in all countries. For this reason, we describe other drugs suitable for mucosal delivery: Captopril and Nitrendipine in the sublingual system and Metoprolol tartrate, Propranolol and Furosemide by the transrectal route. Based on the published data and common clinical practice we discuss the use of mucosal delivery systems of all these antihypertensive drugs with special attention to their pharmacokinetics. We illustrate this mini-review with a case report of the prolonged-term use of mucosal delivery of sublingual Captopril and Nitrendipine combined with rectal Metoprolol tartrate and Furosemide in a patient with severe hypertension unable to receive medication p.o. This is also a report on the first human use of Furosemide-containing suppositories as well as prolonged-term transmucosal administration of these four drugs, describing a practical approach leading to successful control of severe hypertension with four antihypertensive drugs delivered via the mucosal route. The treatment was effective and without side effects; however, the long-term safety and efficacy of such therapy must be confirmed by randomized clinical trials.

• Klíčová slova
• antihypertensive drugs, furosemide, metoprolol, mucosal drug delivery, suppositories,
• MeSH
• antihypertenziva aplikace a dávkování   MeSH
• aplikace sublinguální MeSH
• hypertenze farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• praktické lékařství MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• antihypertenziva MeSH

The transdermal application of actives offers numerous advantages over other conventional routes. Namely, a stable level of drugs in the bloodstream and reduced side effects are the argument for topical administration. Unfortunately, the exceptional skin barrier and unsuitable physico-chemical properties of drugs are the limiting factors for the transdermal passage. It is possible to overcome this by incorporating the drug into nano-carriers to enhance its permeation through the skin barrier. For this purpose, we prepared lipid nanocapsules (LNCs) to modulate skin passage of three pharmaceutically important drugs - indomethacin (IND), diclofenac sodium (DF) and caffeine (CF). We present a stable system prepared by the phase inversion temperature method with particle size under 100 nm and PDI < 0.1 with great encapsulation efficiency for indomethacin and diclofenac. By FTIR it was possible to confirm (for IND and DF) or disprove (in case of CF) the incorporation of a drug into the LNCs. By ex vivo permeation experiments on porcine skin, we confirmed the superior effect of the LNCs on the APIs skin passage. The drug permeated through the skin with higher intensity when delivered from LNCs compared to other standard formulations. We show that lipid nanocapsules play an important role in enhanced topical application of actives.

• Klíčová slova
• Caffeine, Dermal and transdermal delivery, Diclofenac, Indomethacin, Lipid nanocapsules,
• MeSH
• aplikace kožní MeSH
• diklofenak MeSH
• indomethacin MeSH
• lipidy chemie   MeSH
• nanokapsle * chemie   MeSH
• nosiče léků chemie   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• diklofenak MeSH
• indomethacin MeSH
• lipidy MeSH
• nanokapsle * MeSH
• nosiče léků MeSH

OBJECTIVES: The aim of this study was to evaluate and compare the rate of degradation and elimination of praziquantel and fenbendazole antiparasitics following oral administration to salmonids. In addition, we determine whether the length of the legal withdrawal period is sufficient for complete elimination of antiparasitic residue from the body. The use of these drugs in fish is currently considered off-label and data on degradation are not available for rainbow trout. METHODS: The model species for this experiment was the rainbow trout (Oncorhynchus mykiss) and praziquantel and fenbendazole were chosen for experimental therapy. Both drugs were administered into the gastrointestinal tract using a stomach tube. Concentrations of fenbendazole and praziquantel were established through high performance liquid chromatography-tandem mass spectrometry. RESULTS: Our results show that concentrations of praziquantel and fenbendazole reach their maximum in the body within 24 hours of administration, with concentrations dropping sharply over the following 24 hours. With one exception, when trace amounts of both substances were found in blood plasma, the drugs were completely degraded and eliminated from the body by the end of the experiment (corresponding to 497.6 degree days). CONCLUSIONS: Praziquantel and fenbendazole both show a high rate of degradation and elimination from fish. As both substances were eliminated from the body within the required withdrawal period (i.e. within 500 degree days) they can be safely used based on current knowledge of their therapeutic effect for treating helminth infections.

• MeSH
• anthelmintika farmakokinetika   MeSH
• antinematodní látky farmakokinetika   MeSH
• aplikace orální MeSH
• chromatografie kapalinová MeSH
• fenbendazol farmakokinetika   MeSH
• Oncorhynchus mykiss metabolismus   MeSH
• praziquantel farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthelmintika MeSH
• antinematodní látky MeSH
• fenbendazol MeSH
• praziquantel MeSH